Most physiological, biochemical and behavioral events in vertebrates, including man, show significant daily fluctuations; these rhythms are driven by an internal "biological clock(s)." The circadian system of man has important health-related consequences in at least three areas: (1) Abrupt changes in the temporal environment - as experienced by jet travelers or shift workers - can cause disruption of sleep, gastro-intestinal disturbances, and a general feeling of malaise. (2) Certain sleep disorders as well as mental illnesses, such as manic-depressive illness, are thought to reflect inappropriate phase-relationships between internal daily rhythms. (3) The effectiveness of drug therapies, as well as the toxicity of drugs, varies with time-of-day. The proposed studies are designed to elucidate the physiology of the circadian system of a higher vertebrate, using the Japanese quail as a model. The pineal organ, the suprachiasmatic nuclei (SCN) of the hypothalamus, and the eyes have been identified as parts of the circadian "system." The role of these areas will be assessed by surgical manipulation (i.e., pinealectomy, SCN lesions) as well as by measurement, via radioimmunoassay, of a putative hormone (melatonin) which is rhythmically produced in both the pineal and eyes and which is involved in circadian organization. These studies will indicate how these three areas - all of which may be autonomously rhythmic-interact to produce a temporally adapted whole so that the right event occurs at the proper time of day.